Corticotrophin releasing hormone and the timing of birth

Abstract

Corticotrophin-releasing hormone (CRH) is the hypothalamic peptide that controls the function of the pituitary-adrenal axis in response to stress. CRH is also expressed abundantly in the human placenta and is present in high concentrations in maternal and fetal plasma during late pregnancy. During pregnancy, CRH derived from the placenta is thought to play a crucial role in the regulation of fetal maturation and the timing of delivery, and CRH has also been implicated in the control of fetal-placental blood flow. Elevated CRH concentrations, as compared with gestational age matched controls, occur in patients in preterm labour. The exponential curve depicting the CRH increase is shifted to the left in women who will subsequently deliver preterm and to the right in women who will deliver post dates. This has led to the suggestion that CRH production is linked to a placental clock which determines the length of gestation. Clinically, maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may be useful in preventing preterm labour. As significant CRH production by the placenta is restricted to primates, future research must take into account the species specificity of the mechanisms regulating parturition. A number of significant gaps remain in our knowledge of the function of this peptide in pregnancy. This review examines the current evidence regarding the role of CRH in human parturition.